SAM-e

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The contents of the following article are excerpted from "Encyclopedia of Nutritional Supplements", chapter 45, by Michael M. Murray, Copyright ⓒ 1996 by Prima Publishing.
The contents of this page should not be copied, printed, or distributed in any form, unless through a written permission from the publisher, Prima Publishing , P.O. box 1260BK, Rockling, CA 95677.

Food Sources
Deficiency Signs and Symptoms
Beneficial Effects
Available Forms
Principal Uses
Depression
Fibromyalgia
Migraine
Dosage Ranges
Safety Issues and Interactions

S-Adenosylmethionine (SAM) is an important physiological agent formed in the body by combining the essential amino acid methionine with adenosyl-triphosphate (ATP). SAM was discovered in Italy in 1952-- not surprisingly, most of the research on SAM has been conducted in the country of its discovery.

Food Sources
Because SAM is manufactured from methionine, you might think that dietary sources of methionine provide the same benefits as SAM. However, high doses of methionine do not increase levels of SAM, nor do they provide the same pharmacological activity as SAM. On the contrary, high dosages of methionine are associated with some degree of toxicity.

Deficiency Signs and Symptoms
Normally the body manufactures all the SAM it needs from the amino acid methionine. However, a deficiency of methionine, vitamin B12, or folic acid can result in decreased SAM synthesis. In addition, tissue levels of SAM are typically low in the elderly and in patients suffering from osteoarthritis, depression, and various liver disorders.

Beneficial Effects
SAM is involved in over 40 biochemical reactions in the body. It functions closely with folic acid and vitamin B12 in "methylation" reactions--the process of adding a single carbon unit (a metyl group) to another molecule. SAM is many times more effective in transferring methyl groups than other methyl donors. Methylation reactions are critical in the manufacture of many body components--- especially brain chemical --and in detoxification reactions.

SAM is also required in the manufacture of all sulfur-containing compounds in the human body, including glutathione and various sulfur-containing cartilage components. The beneficial effects of SAM supplementation are far-reaching because of its central role in so many metabolic processes.

Available Forms
SAM has been available commercially in Europe since 1975. Unfortunately, as of April 1996, it was still not available in the United States. I discuss it here because I believe it will be into U.S. health-food stores as a nutritional supplement in the very near future. The commercial form of SAM is a stabilized salt produced under U.S. patent numbers 3,954,726 (1976) and 4,057,686 (1977).

Principal Uses
There are five principal conditions where SAM is used: depression, osteoarthritis, fibromyalgia, liver disorders, and migraine headaches.

Depression
SAM is necessary in the manufacture of important brain compounds such as neurotransmitters and phospholipids like phosphatidylcholine and phosphatidylserine. Supplementing the diet with SAM in depressed patients results in increased levels of serotonin, dopamine, and phosphatidylserine. It improves binding of neurotransmitters to receptor sites, which causes increased serotonin and dopamine activity and improved brain cell membrane fluidity, all resulting in significant clinical improvement.

The antidepressive effects of folic acid (Vitamin B6) are mild compared to the effects noted in clinical trials using SAM. Based on results from a number of clinical studies, it appears that SAM is perhaps the most effective natural antidepressant (although a strong argument could be made for the extract of St. John's Wort standardized to contain 0.3 percent hypericin) Tables 45.1 and 45.2 [ following tables ] summarize double-blind studies comparing SAM to either a placebo or an antidepressant drug.

Most of the studies cited in Table 45.1 and 45.2 used injectable SAM. However, more recent studies using a new oral preparation at a dosage of 400 milligrams four times daily (1600 mg total) demonstrate that SAM is just as effective orally as it is intravenously. SAM is better tolerated and has a quicker onset of antidepressant action than tricyclic antidepressants.

The most recent study compared SAM to the tricyclic desipramine. In addition to clinical response, the blood level of SAM was determined in both groups. At the end of the 4-week trial, 62 percent of the patients treated with SAM and 50 percent of the patients treated with desipramine had significantly improved. Regardless of the type of treatment, patients with a 50 percent decrease in their Hamilton Depression Scale (HAM-D) score showed a significant increase in plasma SAM concentration. These results suggests that one of the ways tricyclic drugs exert antidepressive effects is by raising SAM levels.

In addition to generalized depression, there are two conditions associated with depression where SAM produces significant effects: the postpartum (after pregnancy) period and drug rehabilitation. SAM's benefits in these conditions probably stem from a combination of its effects on brain chemistry and liver function. In the study in postpartum depression (after-pregnancy "blues"), the administration of SAM (1,600 milligrams per day) produced significantly better mood scores than a placebo group. As for the use of SAM in drug detoxification, SAM (1,200 milligrams daily) significantly reduced psychological distress (chiefly anxiety and depression) in the detoxification and rehabilitation of opiate abusers.

Fibromyalgia
Fibromyalgia is a recently recognized disorder which is regarded as a common cause of chronic musculoskeletal pain and fatigue. Fibromyalgia shares many common features with another recently termed syndrome, the chronic fatigue syndrome (CFS).
The only difference in diagnostic criteria for fibromyalgia and CFS is the requirement of musculoskeletal pain in fibromyalgia and fatigue in CFS. The likelihood of being diagnosed as having fibromyalgia or CFS depends on the type of physician consulted. Specifically, if the patient consults a rheumatologist or orthopedic specialist, he or she is much more likely to be diagnosed with fibromyalgia than CFSs. Depression is often an underlying finding in both fibromyalgia and CFS.

Diagnosis requires fulfillment of all the following major criteria and four or more minor criteria. The major criteria are:

• Generalized aches or stiffness of at least three anatomic sites for at least three months
  
  
• Six or more typical, reproducible tender points
  
  
• Exclusion of other disorders that can cause similar symptoms

The minor criteria are:

• Generalized fatigue
  
  
• Chronic headache
  
  
• Sleep disturbance
  
  
• Neurological and psychological complaints
  
  
• Joint swelling
  
  
• numbing or tingling sensations
  
  
• Irritable bowel syndrome
  
  
• Variation of symptoms in relation to activity, stress, and weather changes

Three clinical studies show SAM produces excellent benefits in patients suffering from fibromyalgia. The first study was a double-blind, crossover study of 17 patients with fibromyalgia. During treatment with SAM (200 milligrams daily by injection for 21 days), subjects demonstrated significant reduction in the number of trigger points and painful areas and improvements in mood.

In another double-blind study, orally administered SAM (800 milligrams daily) was compared to a placebo for 6 weeks in 44 patients with fibromyalgia. Researchers eval‎uated tender point score, muscle strength, disease activity, subjective symptoms, mood parameters, and side effects. Patients given SAM demonstrated improvements in clinical disease activity, pain experienced during the last week, fatigue, morning stiffness, and mood; however, the tender point score and muscle strength did not differ in the two treatment groups. SAM was without side effects.

The most recent study compared SAM to transutaneous electrical nerve stimulation (TENS)-- a popular treatment for fibromyalgia-- in 30 patients with fibromyalgia. Patients receiving SAM (200 milligrams by injection and 400 milligrams orally daily) demonstrated significantly greater clinical benefits---decreased number of tender points, subjective feelings of pain and fatigue, and improved mood. TENS offered little benefit on most symptoms while SAM was deemed "effective in relieving the signs and symptoms of primary fibromyalgia."

Migraine
SAM is beneficial in the treatment of migraine headaches. The benefits manifest gradually and require long-term treatment for therapeutic effectiveness.

Dosage Ranges
In general, the longer SAM is used, the more beneficial the results. It is perfectly suited for long-term use because of its excellent safety profile. Here are the dosage ranges for the various clinical indications.

• Depression Four hundred milligrams three to four times daily. Because SAM can cause nausea and gastrointestinal disturbances in some people, it should be started at a dosage of 200 milligrams twice daily for the first day, increased to 400 milligrams twice daily on day three, 400 milligrams three times daily on day ten, and finally to the full dosage of 400 milligrams four times daily after 20 days if needed.
  
  
• Fibromyalgia Two hundred milligrams to 400 milligrams two times daily.

Safety Issues
No significant side effects have been reported with oral SAM other than the occasional nausea and gastrointestinal disturbances. However, individuals with bipolar (manic) depression should not take SAM unless under strict medical supervision. SAM's antidepressant activity may lead to the manic phase in these individuals. This effect is exclusive to some individuals with bipolar depression.

Interactions
SAM functions very closely with vitamin B12, folic acid, vitamin B6, and choline in methylation reactions. Because of SAM's effects on the liver, it may enhance the elimination of various drugs from the body. The clinical significance of this particular effect has not been fully determined.

		SAM-e Enteric Coated, Stabilized (H) SAM-e Enteric Coated, Nutralife, 200 mg., 60 Tabs. (T2) SAM-e, Jarrow Formulas, 200 mg, 60 Tabs. SAMe (SAM-e) with B-vitamin, Now Foods, 200 mg, 60 Enteric Coated Tablets SAMe (SAM-e) , Now Foods, 400 mg, 30 Enteric Coated Tablets SAM-e (SAM e), Natrol, 200 mg, 20 Tablets (T2) SAMe (SAM-e) Joint Formula with MSM & Glucosamine, Natrol, 20 Enteric Coated Caplets (H) SAM-e, Source Naturals, 200 mg., 60 Tabs. (H) SAM-e, Source Naturals, 400 mg., 30 Tabs. (T2) SAM-e, Jarrow, 200 mg, 20 Tablets SAM-e, Nutri Plus ( Same as Pharmavite Nature made ), 200 mg., 20 Entric Coated Tablets SAM-e ion, Natural Factors, 200 mg, 30 Tablets (Enteric Coated)				SAM-e Boosters Folic Acid, B6, B12, and TMG Combinations ( SAM-e Booster ) Homocysteine Defense, Source Naturals, 120 Tabs. ( SAM-e Booster ) Homocysteine Shield, BioChem, Country Life, 60 Tablets SAM-e

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